Alteration of growth responses in established cardiac pressure overload hypertrophy in rats with aortic banding

被引：53

作者：

Schunkert, H

Weinberg, EO

Bruckschlegel, G

Riegger, AJG

Lorell, BH

机构：

[1] HARVARD UNIV, BETH ISRAEL HOSP,SCH MED,HARVARD THORNDIKE LAB, DEPT INTERNAL MED,DIV CARDIOVASC, BOSTON, MA 02215 USA

[2] HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, CHARLES A DANA RES INST, BOSTON, MA 02215 USA

[3] UNIV REGENSBURG, INNERE MED KLIN & POLIKLIN 2, D-93042 REGENSBURG, GERMANY

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1995年 / 96卷 / 06期

关键词：

hypertrophy; rat; protooncogene; angiotensin; norepinephrine;

D O I：

10.1172/JCI118346

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

We examined the acute effects of elevated wall stress, norepinephrine, and angiotensin II on cardiac protein synthesis as well as protooncogene expression in hearts with established pressure overload left ventricular hypertrophy, Isolated fat hearts with chronic hypertrophy (LVH) were studied 12 wk after ascending aortic banding when systolic function was fully maintained, New protein synthesis (incorporation of [H-3]phenylalanine [Phe]) was analyzed in isolated perfused rat hearts after a 3-h protocol; c-fos, c-jun, c-myc, and early growth response gene-1 (EGR-1) mRNA levels (Northern blot) were studied over a time course from 15 to 240 min of perfusion, Under baseline conditions (i.e., before mechanical or neurohormonal stimulation), [N-3]Phe-incorporation (280 nmoles/gram protein/h) and protooncogene mRNA levels were similar in age-matched control and LVH hearts. However, hearts with chronic LVH were characterized by a markedly blunted or absent [3H]Phe-incorporation after acute imposition of isovolumic systolic load(90 mmsg/gram left ventricle), as well as norepinephrine(10(-6) NI), or angiotensin II infusion (10(-8) M plus prazosin 10(-7) NI) compared with nonhypertrophied control hearts, Similarly, stimulation of LVH hearts with acute systolic load or norepinephrine was associated with a significantly blunted increase of protooncogene mRNA levels relative to control hearts, The blunted induction of c-fos mRNA in LVH hearts was not due to feedback inhibition, since cycloheximide perfusion of hearts exposed to elevated wall stress further increased the differences between age-matched control and LVH hearts. The data suggest that acute molecular growth responses to mechanical or neurohormonal stimulation are altered in rat hearts with established LVH relative to nonhypertrophied control hearts, This alteration of molecular adaptations in hearts with compensatory hypertrophy may prevent inappropriate excess cardiac growth in response to mechanical and neurohormonal stimuli.

引用

页码：2768 / 2774

页数：7

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